A Decade of Electrochemical Dehydrogenative C,C-Coupling of Aryls

Abstract

The importance of sustainable and green synthetic protocols for the synthesis of fine chemicals has rapidly increased during the last decades in an effort to reduce the use of fossil fuels and other finite resources. The replacement of common reagents by electricity provides a cost-and atom-efficient, environmentally friendly, and inherently safe access to novel synthetic routes. The selective formation of carbon− carbon bonds between two distinct substrates is a crucial tool in organic chemistry. This fundamental transformation enables access to a broad variety of complex molecular architectures. In particular, the aryl−aryl bond formation has high significance for the preparation of organic materials, drugs, and natural products. Besides well-known and well-established reductive-and oxidative-reagent-mediated or transition-metal-catalyzed coupling reactions, novel synthetic protocols have arisen, which require fewer steps than conventional synthetic approaches. Electroorganic conversions can be categorized according to the nature of the electron transfer processes occurring. Direct transformations at inert electrode materials are environmentally benign and cost-effective, whereas catalytic processes at active electrodes and mediated electrosynthesis using an additional soluble reagent can have beneficial properties in terms of selectivity and reactivity. In general, these conversions require challenging optimization of the reaction parameters and the appropriate cell design. Galvanostatic reactions enable fast conversions with a rather simple setup, whereas potentiostatic electrolysis may enhance selectivity. This Account discusses the development of seminal carbon−carbon bond formations over the past two decades, focusing on phenols leading to precursors for ligands in, e.g., hydroformylation reaction. A key element in the success of these electrochemical transformations is the application of electrochemically inert, non-nucleophilic, highly fluorinated alcohols such as 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), which exhibit a large potential window for transformations and enable selective cross-coupling reactions. This selectivity is based on the capability of HFIP to stabilize organic radicals. Inert, carbon-based and metal-free electrode materials like graphite or boron-doped diamond (BDD) open up novel electroorganic pathways. Furthermore, novel active electrode materials have been developed to enable intra-and intermolecular dehydrogenative coupling reactions of electron-rich aryls. The application of 2,2′-biphenol derivatives as ligand components for catalysts requires reactions to be carried out on larger scale. In order to achieve this, continuous flow transformations have been established to overcome the drawbacks of heat transfer, overconversion, and conductivity. Modular cell designs enable the transfer of a broad variety of electroorganic conversions into continuous processes. Recent results demonstrate the application of organic electrochemistry to natural product synthesis of the pharmaceutically...

Synthesis of a Bcl9 Alpha-Helix Mimetic for Inhibition of PPIs by a Combination of Electrooxidative Phenol Coupling and Pd-Catalyzed Cross Coupling

“…Consequently, this method requires no stoichiometric reagents. Currently, this methodology exhibits the lowest environmental impact and is considered as inherently safe [21][22][23][24]. Upon conversion of the biphenols into sulfonate esters, these structure motifs could be connected with pyridine boronic acids via Pd-catalyzed cross-coupling reactions.…”

Electrosynthesis 2.0 in 1,1,1,3,3,3‐Hexafluoroisopropanol/Amine Mixtures

“…It consists of a two-step sequence and the HFIP ether generated in-situ can be used without further purification. The reaction is selective with yields up to 90 % over 2 steps and methoxy groups (18), multiple alkyl groups (19), propyl moieties (20) and halogens (21) being tolerated (Scheme 5). Phenols can be converted in a protective group- free manner, shortening the usual synthetic route by one or two steps.…”

“…[15,16] HFIP has demonstrated superior effects compared to other solvents when it comes to improving selectivity and yield of various electrochemical transformations. [17][18][19][20][21] In particular, the solvate formation modulates nucleophilicity and oxidation potential. [7,17] The unusual electrochemical stability of HFIP is ensured as long as inert anodes are employed for direct electrode processes, [22] whereas hypervalent iodine mediators are capable to convert HFIP to highly toxic hexafluoroacetone.…”

“…[24] Electrochemistry has experienced a renaissance in recent years since it offers benefits over classical synthetic methodologies. [18][19][20]28] Electric current, as an inexpensive and inherently safe reagent, facilitates sustainable synthetic pathways, and is compatible with renewable energy sources. [29] A direct contribution for the stabilizing of the electric grid is provided, when the electro-conversions are robust and fluctuating electricity can be employed without loss of selectivity and reactivity.…”

Topological Dynamics of a Radical Ion Pair: Experimental and Computational Assessment at the Relevant Nanosecond Timescale

“…These methodologies generally involve the formation of charged species. Here, ion pairing plays an important role in solution, as indicated in recent publications [1][2][3][4]. The important role of ion pairing extends in fields like catalysis [5], organic synthesis [6][7][8], and the chemistry of flavonoids [9,10] and radical-induced DNA-strand breaks [11].…”